Cervical cancer remains one of the leading causes of cancer-related mortality among women worldwide. In 2018, an estimated 570,000 new cases and 311,000 deaths attributable to cervical cancer were reported globally, with approximately 85 per cent of these deaths occurring in developing or under-resourced settings¹. It ranks second in incidence and mortality among cancers in women in low Human Development Index settings, and is the most frequently diagnosed cancer in 28 countries and the leading cause of cancer death in 42 countries².

Persistent infection with high-risk human papillomavirus (HPV) subtypes, detectable in nearly all cervical cancer specimens, is the principal aetiological driver; genotypes 16 and 18 alone account for approximately 70 per cent of invasive disease worldwide³. Clinical staging has traditionally followed the International Federation of Gynaecology and Obstetrics (FIGO) system; the 2018 revision explicitly incorporated imaging findings into stage assignment, reflecting growing recognition that anatomical staging alone is insufficient for guiding management decisions⁴.

Combined FDG PET-CT integrates metabolic and anatomical information and has demonstrated higher sensitivity and specificity than conventional cross-sectional imaging for detecting loco-regional nodal disease and distant metastases in cervical cancer⁵⁶. By identifying disease outside the volumes typically covered by conventional radiotherapy fields — for example, para-aortic or inguinal nodal involvement — PET-CT can directly influence target volume delineation, prescribed dose, and the decision to extend fields or deliver nodal boosts⁷⁸. Serial PET-CT has additionally been used to monitor metabolic response during and after chemoradiation, with prognostic implications for disease-free and overall survival⁹.

Multiple studies from varied settings have reported that PET-CT alters FIGO stage and radiotherapy plans in a meaningful proportion of patients with cervical carcinoma¹⁰⁻¹⁵. Updated ESGO/ESTRO/ESP guidelines recommend PET-CT before curative-intent chemoradiation in locally advanced cervical cancer with node-positive or bulky disease¹⁶. However, data from Indian tertiary care settings, where disease burden and stage at presentation often differ from those informing current international practice, remain limited. This study was undertaken to determine, in a cohort of patients with cervical carcinoma stage IB2–IVA planned for curative-intent radiotherapy at a tertiary cancer centre in southern India, (i) the proportion of patients restaged after PET-CT relative to conventional clinical/radiological staging, and (ii) the proportion of patients whose radiotherapy plan was modified based on PET-CT findings.

Study design and setting This was an ambispective (retrospective and prospective) observational study conducted in the Department of Radiation Oncology, Nizam's Institute of Medical Sciences (NIMS), Hyderabad, India. Records of patients treated between 2018 and 2023 were retrieved and analysed retrospectively; patients treated between December 2023 and January 2025 were recruited prospectively. The study protocol was approved by the NIMS Institutional Ethics Committee (Review letter No. EC/NIMS/3524/2024, 85th ESGS No. 1760/2024, dated 25 October 2024). Written informed consent was obtained from all prospectively enrolled participants. Study population and sample size Patients with histopathologically confirmed cervical carcinoma of clinical stage IB2–IVA (FIGO) who underwent 18F-FDG PET-CT for radiotherapy planning and were treated with curative intent were eligible. A total of 50 patients were included — 19 retrospectively and 31 prospectively. Inclusion criteria (i) Patients with histopathologically confirmed cervical carcinoma, clinical stage IB2 to IVA, planned for radiotherapy with curative intent; and (ii) patients who underwent 18F-FDG PET-CT for radiation treatment planning. Exclusion criteria (i) Patients with metastatic or recurrent cervical carcinoma planned for palliative treatment; and (ii) patients who underwent surgery for cervical cancer. Pre-PET-CT work-up and PET-CT protocol All patients underwent detailed clinical examination and baseline imaging with CT, MRI, or ultrasonography prior to radiation planning. PET-CT was subsequently performed as per the standard protocol of the Department of Nuclear Medicine, NIMS. Patients fasted overnight for a minimum of 6 hours; random blood glucose was required to be below 200 mg/dL and serum creatinine below 1.4 mg/dL. An intravenous dose of 6–12 mCi of 18F-FDG was administered, and imaging was performed approximately 45 minutes after tracer injection, acquiring images from the base of skull to mid-thigh at a slice thickness of 1.25 mm. In patients with clinically or radiologically detected hydroureteronephrosis, non-contrast PET-CT was performed instead of standard contrast-enhanced PET-CT to avoid the risk of contrast-induced nephropathy in the setting of potential underlying renal impairment. Radiotherapy planning For the prospective cohort, patients underwent thermoplastic pelvic immobilisation casting with external fiducial markers for isocentre localisation, followed by PET-CT in the treatment position on a flat couch. PET-CT images were transferred to the treatment planning system (Varian Eclipse™, version 15.5), and three-dimensional conformal radiotherapy (3D-CRT) plans were generated. Nodal contouring followed the guidelines proposed by Taylor et al²⁵. The indication for elective para-aortic irradiation was based on the number of PET-positive level 1 pelvic lymph nodes (more than 2 positive nodes); elective para-aortic irradiation was also applied when even one positive node was identified at level 2 (common iliac) or above, in keeping with ESGO/ESTRO/ESP guidance¹⁶. When the lower third of the vagina was involved, the groin was additionally included in the elective target volume. Study variables and endpoints Clinical stage assigned prior to PET-CT (based on clinical examination and CT/MRI/USG) was recorded and compared with stage after incorporation of PET-CT findings. The radiotherapy plan generated using conventional staging information was compared with the final plan after PET-CT review, and any modification — including extension of the treatment field to include the para-aortic region, addition of a nodal boost, or change in prescribed dose — was documented. The two pre-specified study endpoints were: (i) the proportion of patients restaged after PET-CT, and (ii) the proportion of patients whose RT plan was modified based on PET-CT findings. Data collection A structured proforma was used to record demographic details, comorbidities, personal, past, family, marital, menstrual and obstetric history, histopathological details, pre- and post-PET-CT clinical stage, details of RT plan modification, brachytherapy details, chemotherapy details, treatment dates, dose-fractionation schedule, whether the field was extended to include para-aortic nodes, boost details, and follow-up status. Statistical analysis Data were tabulated in Microsoft Excel 2019 (Windows Inc.) and analysed descriptively using SPSS version 22.0 (IBM Corp.). Categorical variables were expressed as frequencies and percentages; continuous variables were expressed as median

Fifty patients were included in the study — 31 recruited prospectively and 19 analysed retrospectively. The median age at diagnosis was 56.5 years. Of the 50 patients, 6 (12%) were pre-menopausal and 44 (88%) were post-menopausal.

Baseline characteristics

Comorbidities were present in a minority of patients: Hypertension alone in 4 patients, Hypertension with Diabetes mellitus in 5, Diabetes mellitus alone in 3, and active abdominal Tuberculosis in 1 patient. On histopathology, 48 patients (96%) had Squamous cell carcinoma and 2 (4%) had adenocarcinoma.

Table I. Baseline characteristics of study patients (N=50)

Fig. 1. Menopausal status of study patients (N=50).

Fig. 2. Histological variant of cervical carcinoma (N=50).

Stage migration after PET-CT

Table II compares the FIGO stage distribution based on conventional clinical/MRI/CT/USG assessment with the distribution based on PET-CT. On conventional staging, the largest groups were stage IIIB (14 patients, 28%) and IIIC1 (10 patients, 20%); no patient was classified as stage IVB. On PET-CT-based staging, the largest groups shifted to stage IIIC1 (15 patients, 30%) and IIIC2 (12 patients, 24%), and 4 patients (8%) were reclassified as stage IVB based on detection of distant metastatic disease not apparent on conventional imaging.

Table II. FIGO stage distribution: conventional staging versus PET-CT-based staging (N=50)

Fig. 3. FIGO stage distribution based on PET-CT scan (N=50).

Overall, 22 patients (44%) were upstaged based on PET-CT findings, while 28 patients (56%) had no change in stage (Table III). Four patients (8%) were found to have distant metastatic disease on PET-CT that had not been identified on conventional imaging.

Table III. Proportion of patients restaged after PET-CT (N=50)

Fig. 4. Proportion of patients upstaged after PET-CT (N=50).

Modification of radiotherapy plan

The RT plan was modified based on PET-CT findings in 15 patients (30%); the remaining 35 patients (70%) required no change to the treatment plan (Table IV). Among the modifications, the treatment field was extended to include the para-aortic lymph nodes in 19 patients (38%) (Table V).

Table IV. RT plan modification based on PET-CT findings (N=50)

Fig. 5. Modification of radiotherapy plan based on PET-CT findings (N=50).

Table V. Treatment field extension to include para-aortic lymph nodes (N=50)

Fig. 6. Treatment field extension to include para-aortic lymph nodes (N=50).

A lymph node boost was delivered in 14 patients (28%): para-aortic nodes alone in 6 patients (12%), iliac nodes alone in 7 patients (14%), and both para-aortic and iliac nodes in 1 patient (2%) (Table VI).

Table VI. Site of lymph node boost among patients receiving a boost (N=50)

Fig. 7. Site of lymph node boost among patients receiving a boost (N=50).

PET-CT technique modification and treatment details

Eleven patients (22%) had hydroureteronephrosis detected on clinical or radiological assessment; non-contrast PET-CT was performed in these patients instead of standard contrast-enhanced PET-CT to avoid the risk of contrast-induced nephropathy in the setting of potential underlying renal impairment.

Thirty-one patients (62%) received concurrent chemotherapy with weekly cisplatin at 40 mg/m² during radiation treatment.

Cervical cancer is one of the leading causes of cancer death among females. Initial staging has traditionally relied on integrated data from physical examination, CT, and MRI, which offer high anatomic resolution; PET-CT has since become an established complementary imaging modality for the evaluation of cervical cancer. In the present study, PET-CT altered clinical stage in 44 per cent of patients and modified the radiotherapy plan in 30 per cent — findings that are broadly consistent with both Indian and international literature. Loft and colleagues²¹ conducted a prospective study among 120 patients to determine the clinical value of PET-CT as a supplement to FIGO staging in patients with cervical cancer stage greater than IB. Metastatic disease was found in 10 of 119 patients, with a sensitivity of 100 per cent and specificity of 94 per cent; [18F]FDG-PET-CT had a positive predictive value of 75 per cent and negative predictive value of 96 per cent for pelvic nodal disease. They concluded that whole-body FDG PET-CT is a valuable supplement to FIGO staging. In the present study, PET-CT enabled detection of para-aortic lymph node involvement in 38 per cent (19 of 50) of cases, leading to field extension in radiation planning; updated ESGO/ESTRO/ESP guidelines recommend elective para-aortic irradiation based on nodal status, and PET-CT facilitated this decision-making by accurately identifying nodal spread¹⁶. Amit et al²², in a study of 75 patients with cervical cancer evaluated with pre-treatment PET-CT, found improved diagnosis in 43 per cent of patients and concluded that PET-CT reduces surgical interventions and helps in better radiation field planning. In the present study, 44 per cent of patients (22 of 50) were upstaged based on PET-CT findings, a rate comparable to that reported by Amit et al. Lin et al²³, in a retrospective study of 1158 consecutively evaluated patients with cervical cancer between 1997 and 2017, reported that 72 patients (6.2%) had FDG-avid distant disease at diagnosis, and that patients with multiple sites of distant disease had the worst overall survival. In the present study, 4 patients (8%) had distant metastases detected on PET-CT that were not identified on other imaging modalities, consistent with the importance of PET-CT, compared with conventional imaging, in detecting distant metastatic disease. In the present study, a lymph node boost was administered in 28 per cent (14 of 50) of patients, with the majority involving para-aortic nodes. Rash et al²⁴ evaluated the threshold for clinical dose response for para-aortic and pelvic lymph node boosts using imaging (CT and FDG-PET) and clinical outcomes in 68 patients with locally advanced cervical cancer, of whom 40 had clinically involved para-aortic and/or pelvic lymph nodes; a radiation boost dose of 0–15 Gy (mean total dose 52.3 Gy) resulted in a decrease in SUV in all treated nodes, with complete resolution in 68 per cent. This supports the use of PET-CT-guided nodal boosts to personalise treatment and potentially improve loco-regional control. Grigsby et al²⁵, in a retrospective study of 101 patients with newly diagnosed cervical cancer, demonstrated that FDG-PET-determined lymph node status is the most significant independent pre-treatment predictor of progression-free and overall survival, and that FDG-PET is superior to CT in detecting abnormal nodes and predicting treatment outcomes. This underscores the potential prognostic value of the nodal information obtained by PET-CT in the present cohort, although survival correlation was outside the scope of the present analysis. Belhocine et al²⁶, in a study of 60 patients with cervical cancer, found that whole-body PET altered management in 18 per cent of the study population, either through modulation of the radiation field to include the para-aortic area or through a change in total dose. The 30 per cent RT-plan modification rate observed in the present study is somewhat higher, which may reflect differences in baseline stage distribution, since a substantial proportion of the present cohort presented with advanced nodal disease (stage IIIC1/IIIC2 together accounting for 54% of patients on PET-CT staging). Narayan et al²⁷ concluded that PET-CT had a positive predictive value of 91 per cent for depicting pelvic and para-aortic nodes, sufficient to eliminate the need for surgical lymph node sampling and to delineate the radiation field without surgical intervention, while MRI was found to be insufficiently accurate for nodal staging. Ruan et al²⁸, in a meta-analysis of 27 studies published between 2000 and 2017, reported a pooled sensitivity of 0.80 and specificity of 0.87 for PET-CT in detecting pelvic lymph node metastases on a patient basis, summarising that PET-CT has moderate sensitivity and high specificity for this purpose. Concurrent chemoradiotherapy remains the standard of care for locally advanced cervical carcinoma; in the present study, 62 per cent (31 patients) received cisplatin-based concurrent chemotherapy. PET-CT-based staging may additionally help identify patients most likely to benefit from intensified therapy, or conversely those who might require treatment modification due to extensive disease burden or comorbidities such as hydroureteronephrosis, which necessitated non-contrast PET-CT in 22 per cent of the present cohort to avoid contrast-induced nephropathy. Taken together, these findings support the role of PET-CT as a valuable tool in the diagnosis, staging, and radiation treatment planning of cervical carcinoma. PET-CT can detect regional lymph node involvement and extra-pelvic disease extension, is helpful in the detection of distant metastases, and can meaningfully change both clinical stage and treatment plan in patients with cervical cancer. Limitations A key limitation of this study is the lack of pathological confirmation of nodal status, since most patients with locally advanced cervical cancer are planned for non-surgical treatment with chemoradiation, making clinical and radiological determination of stage of paramount importance. Additional limitations include the single-centre design, the ambispective structure (with the retrospective component subject to variability in historical documentation), the modest sample size, and the absence of survival or loco-regional control outcome data, which would require longer follow-up.

PET-CT was useful in the staging of cervical cancer and in radiation treatment planning in this cohort, leading to restaging in 44 per cent and RT plan modification in 30 per cent of patients. PET-based radiation planning, through more accurate delineation of nodal and metastatic disease, may translate into improved tumour control rates and merits wider incorporation into pre-treatment work-up for locally advanced cervical carcinoma in resource-appropriate settings.

Acknowledgements

The authors thank the Department of Nuclear Medicine, NIMS, Hyderabad, for PET-CT acquisition, and the technologists and nursing staff of the Department of Radiation Oncology for their assistance in the conduct of this study.

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